PROVINDA Plus is prescribed for treatment of high blood pressure (hypertension) and/or treatment of stable coronary artery disease (a condition where the blood supply to the heart is reduced or blocked).

Patients already taking perindopril and amlodipine from separate tablets may instead receive one tablet of PROVINDA Plus which contains both ingredients.

PROVINDA Plus is a combination of two active ingredients, perindopril and amlodipine.

Perindopril is an ACE (angiotensin converting enzyme) inhibitor. Amlodipine is a calcium antagonist (which belongs to a class of medicines called dihydropyridines). Together they work to widen and relax the blood vessels so that blood passes through them more easily and makes it easier for your heart to maintain a good blood flow.

Do not take PROVINDA Plus

-           if you are allergic to perindopril or any other ACE inhibitor, or to amlodipine or any other calcium antagonists, or any of the other ingredients of this medicine (listed in Section 6),

-           if you are more than 3 months pregnant (It is also better to avoid PROVINDA Plus in early pregnancy – see pregnancy section),

-           if you have experienced symptoms such as wheezing, swelling of the face or tongue, intense itching or severe skin rashes with previous ACE inhibitor treatment or if you or a member of your family have had these symptoms in any other circumstances (a condition called angioedema),

-           if you have diabetes or impaired kidney function and you are treated with a blood pressure lowering medicine containing aliskiren,

-           if you have narrowing of the aortic heart valve (aortic stenosis) or cardiogenic shock (a condition where your heart is unable to supply enough blood to the body),

-           if you have severe low blood pressure (hypotension),

-           if you suffer from heart failure after a heart attack,

-           if you are having dialysis or any other type of blood filtration. Depending on the machine that is used, PROVINDA Plus may not be suitable for you,

-           if you have kidney problems where the blood supply to your kidneys is reduced (renal artery stenosis),

·       if you are being treated with sacubitril/valsartan, a medicine for heart failure. (see “Warning and Precaution” and “Other medicines and PROVINDA Plus”)

 Take special care with PROVINDA PLUS

If you have any of the following please talk to your doctor, pharmacist or nurse before taking PROVINDA Plus:

-           Hypertrophic cardiomyopathy (cardiac muscle disease) or renal artery stenosis (narrowing of the artery which supplies the kidney with blood),

-           Heart failure,

-           Severe increase in blood pressure (hypertensive crisis),

-           Any other heart problems,

-           Liver problems,

-           Kidney problems or if you are receiving dialysis,

-           Abnormally increased levels of a hormone called aldosterone in your blood (primary aldosteronism),

-           Collagen vascular disease (disease of the connective tissue) such as systemic lupus erythematosus or scleroderma,

-           Diabetes,

-           If you are on a salt restricted diet or use salt substitutes which contain potassium (a well balanced potassium blood level is essential),

-           If you are elderly and your dose needs to be increased,

-           if you are taking any of the following medicines used to treat high blood pressure:

o   An “angiotensin II receptor blocker” (ARBs) (also known as sartans - for example valsartan, telmisartan, irbesartan), in particular if you have diabetes-related kidney problems.

o   Aliskiren.

Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (e.g. potassium) in your blood at regular intervals.

See also information under the heading “Do not take PROVINDA Plus”.

-           Are taking any of the following medicines, the risk of angioedema is increased:

-           Racecadotril (used to treat diarrhea),

-           Sirolimus, everolimus, temsirolimus and other drugs belonging to the class of so-called mTor inhibitors (used to avoid rejection of transplanted organs),

-           Sacubitril (available as fixed dose combination with valsartan) used to treat long-term heart failure.

-           Are of black origin since you may have a higher risk of angioedema and this medicine may be less effective in lowering your blood pressure than in non-black patients.

 Angioedema

Angioedema (a severe allergic reaction with swelling of the face, lips, tongue or throat with difficulty in swallowing or breathing) has been reported in patients treated with ACE inhibitors, including PROVINDA Plus. This may occur at any time during treatment. If you develop such symptoms, you should stop taking PROVINDA Plus and see a doctor immediately. See also section 4.

 You must tell your doctor if you think you are (or might become) pregnant. PROVINDA Plus is not recommended in early pregnancy, and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to your baby if used at that stage (see pregnancy section).

When you are taking PROVINDA Plus, you should also inform your doctor or the medical staff if you:

-           Are going to have a general anaesthetic and/or major surgery,

-           Have recently suffered from diarrhoea or vomiting (being sick),

-           Are to undergo LDL apheresis (the removal of cholesterol from your blood by a machine),

-           Are going to have desensitisation treatment to reduce the effects of an allergy to bee or wasp stings.

 Children and adolescents

 PROVINDA Plus is not recommended for use in children and adolescents.

 Taking other medicines, herbal or dietary supplements

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

 You should avoid PROVINDA Plus with:

-           Lithium (used to treat mania or depression),

-           Estramustine (used in cancer therapy),

-           Potassium-sparing drugs (triamterene, amiloride), potassium supplements or potassium-containing salt substitutes, other drugs which can increase potassium in your body (such as heparin and co-trimoxazole also known as trimethoprim/sulfamethoxazole),

-           Potassium-sparing drugs used in the treatment of heart failure: eplerenone and spironolactone at doses between 12.5 mg to 50 mg by day.

 Treatment with PROVINDA Plus can be affected by other medicines. Your doctor may need to change your dose and/or to take other precautions. Make sure to tell your doctor if you are taking any of the following medicines as special care may be required:

-           Other medicines for high blood pressure, including angiotensin II receptor blocker (ARB), aliskiren (see also information under the headings “Do not take PROVINDA Plus” and “Take special care with PROVINDA Plus”), or diuretics (medicines which increase the amount of urine produced by the kidneys),

-           Medicines, which are most often used to treat diarrhea (racecadotril) or avoid rejection of transplanted organs (sirolimus, everolimus, temsirolimus and other drugs belonging to the class of so-called mTor inhibitors). See section “Warnings and precautions”,

-           Sacubitril/valsartan (used to treat long-term heart failure). See sections “Do not take PROVINDA Plus” and “Warnings and precautions”.

-           Non-steroidal anti-inflammatory drugs (e.g. ibuprofen) for pain relief or high dose aspirin,

-           Medicines to treat diabetes (such as insulin),

-           Medicines to treat mental disorders such as depression, anxiety, schizophrenia etc (e.g. tricyclic antidepressants, antipsychotics, imipramine-like antidepressants, neuroleptics),

-           Immunosuppressants (medicines which reduce the defence mechanism of the body) used for the treatment of auto-immune disorders or following transplant surgery (e.g. ciclosporine, tacrolimus),

-           Trimethoprim and Co-trimoxazole (for the treatment of infections),

-           Allopurinol (for the treatment of gout),

-           Procainamide (for the treatment of an irregular heart beat),

-           Vasodilators including nitrates (products that widen the blood vessels),

-           Ephedrine, noradrenaline or adrenaline (medicines used to treat low blood pressure, shock or asthma),

-           Baclofen or dantrolene (infusion) both used to treat muscle stiffness in diseases such as multiple sclerosis; dantrolene is also used to treat malignant hyperthermia during anaesthesia (symptoms including very high fever and muscle stiffness),

-           Some antibiotics such as rifampicin, erythromycin, clarithromycin (for infection caused by bacteria),

-           Hypericum perforatum (St John’s wort, an herbal medicine used to treat depression),

-           Simvastatin (cholesterol lowering medicine),

-           Antiepileptic agents such as carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone,

-           Itraconazole, ketoconazole (medicines used for treatment of fungal infections),

-           Alpha-blockers used for the treatment of enlarged prostate such as prazosin, alfuzosin, doxazosin, tamsulosin, terazosin,

-           Amifostine (used to prevent or reduce side effects caused by other medicines or radiation therapy that are used to treat cancer),

-           Corticosteroids (used to treat various conditions including severe asthma and rheumatoid arthritis),

-           Gold salts, especially with intravenous administration (used to treat symptoms of rheumatoid arthritis),

-           Ritonavir, indinavir, nelfinavir (so called protease inhibitors used to treat HIV).

 Taking PROVINDA PLUS with food and drink

PROVINDA Plus should be taken before a meal.

Grapefruit juice and grapefruit should not be consumed by people who are taking PROVINDA Plus. This is because grapefruit and grapefruit juice can lead to an increase in the blood levels of the active ingredient amlodipine, which can cause an unpredictable increase in the blood pressure lowering effect of PROVINDA Plus.

 Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

You must tell your doctor if you think you are (or might become) pregnant. Your doctor will normally advise you to stop taking PROVINDA Plus before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of PROVINDA Plus. PROVINDA Plus is not recommended in early pregnancy, and must not be taken when more than 3 months pregnant, as it may cause serious harm to your baby if used after the third month of pregnancy.

Breast-feeding

Amlodipine has been shown to pass into breast milk in small amounts. Tell your doctor if you are breast-feeding or about to start breast-feeding. PROVINDA Plus is not recommended for mothers who are breast-feeding, and your doctor may choose another treatment for you if you wish to breast-feed, especially if your baby is newborn, or was born prematurely.

 Driving and using machines

PROVINDA Plus may affect your ability to drive or use machines. If the tablets make you feel sick, dizzy, weak or tired, or give you a headache, do not drive or use machines and contact your doctor immediately.

 PROVINDA Plus contains lactose monohydrate

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

-           Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

-           Swallow your tablet with a glass of water, preferably at the same time each day, in the morning, before a meal. Your doctor will decide on the correct dose for you. This will normally be one tablet per day.

-           PROVINDA Plus will usually be prescribed for patients already taking perindopril and amlodipine from separate tablets.

 Use in children and adolescents

Use in children and adolescents is not recommended.

 If you take more PROVINDA Plus than you should

If you take too many tablets, contact your nearest accident and emergency department or tell your doctor immediately. The most likely effect in case of overdose is low blood pressure which can make you feel dizzy or faint. If this happens, lying down with your legs raised can help.

 If you forget to take PROVINDA Plus

It is important to take your medicine every day as regular treatment works better. However, if you forget to take a dose of PROVINDA PLUS, take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose.

If you stop taking PROVINDA Plus

As the treatment with PROVINDA Plus is usually life-long, you should discuss with your doctor before you stop taking your tablets.

If you have any further questions on the use of this medicine, ask your doctor, or pharmacist or nurse.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you experience any of the following, stop taking the medicinal product at once and tell your doctor immediately:

-           Sudden wheeziness, chest pain, shortness of breath, or difficulty in breathing,

-           Swelling of eyelids, face or lips,

-           Swelling of the tongue and throat, which causes great difficulty breathing,

-           Severe skin reactions including intense skin rash, hives, reddening of the skin over your whole body, severe itching, blistering, peeling and swelling of the skin, inflammation of mucous membranes (Stevens Johnson Syndrome, Toxic Epidermal Necrolysis) or other allergic reactions,

-           Severe dizziness or fainting,

-           Heart attack, unusual fast or abnormal heart beat, or chest pain,

-           Inflamed pancreas which may cause severe abdominal and back pain accompanied with feeling very unwell.

The following common side effects have been reported. If any of these cause you problems or if they last for more than one week, you should contact your doctor.

-        Very common side effects (may affect more than 1 in 10 people): oedema (fluid retention).

-        Common side effects (may affect up to 1 in 10 people): headache, dizziness, sleepiness (especially at the beginning of treatment), vertigo, numbness or tingling sensation in your limbs, vision disturbances (including double vision), tinnitus (sensation of noises in the ears), palpitations (awareness of your heartbeat), flushing, light-headedness due to low blood pressure, cough, shortness of breath, nausea (feeling sick), vomiting (being sick), abdominal pain, taste disturbances, dyspepsia or difficulty of digestion, change of bowel habit, diarrhoea, constipation, allergic reactions (such as skin rashes, itching), muscle cramps, tiredness, weakness, ankle swelling (oedema peripheral).

Other side effects that have been reported include the following list. If any of these get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

-        Uncommon side effects (may affect to 1 in 100 people): mood swings, anxiety, depression, sleeplessness, sleep disturbances, trembling, fainting, loss of pain sensation, irregular heartbeat, rhinitis (blocked up or runny nose), hair loss, red patches on skin, skin discoloration, back pain, arthralgia (joint pain), myalgia (muscle pain), chest pain, disorder in passing urine, increased need to urinate at night, increased number of times of passing urine, pain, feeling unwell, bronchospasm (tightening of the chest, wheezing and shortness of breath), dry mouth, angioedema (symptoms such as wheezing, swelling of the face or tongue), formation of blister clusters over the skin, kidney problems, impotence, increased sweating, an excess of eosinophils (a type of white blood cells), discomfort or enlargement of the breasts in men, weight increase or decrease, tachycardia, vasculitis (inflammation of blood vessels), photosensitivity reaction (increased sensitivity of the skin to sun), fever, fall, change in laboratory parameters: high blood level of potassium reversible on discontinuation, low level of sodium, hypoglycaemia (very low blood sugar level) in case of diabetic patients, increased blood urea, and increased blood creatinine.

-        Rare side effects (may affect up to 1 in 1000 people): confusion, psoriasis worsening, changes in laboratory parameters: increased level of liver enzymes, high level of serum bilirubin.

-    Very rare side effects (may affect up to 1 in 10,000 people): cardiovascular disorders (angina, heart attack and stroke), eosinophilic pneumonia (a rare type of pneumonia), swelling of eyelids, face or lips, swelling of the tongue and throat, which causes great difficulty in breathing, severe skin reactions including intense skin rash, hives, reddening of the skin over your whole body, severe itching, blistering, peeling and swelling of the skin, inflammation of mucous membranes (Stevens Johnson Syndrome), erythema multiforme (a skin rash which often starts with red itchy patches on your face, arms or legs), sensitivity to light, changes in blood values such as a lower number of white and red blood cells, lower haemoglobin, lower number of blood platelets, disorders of the blood, inflamed pancreas which may cause severe abdominal and back pain accompanied with feeling very unwell, acute renal failure, abnormal liver function, inflammation of the liver (hepatitis), yellowing of the skin (jaundice), liver enzyme increase which may have an effect on some medical tests, abdominal bloating (gastritis), disorder of the nerves which can cause weakness, tingling or numbness, increased muscle tension, swelling of the gums, excess sugar in blood (hyperglycaemia).

-        Frequency not known (frequency cannot be estimated from the available data):

-        Trembling, rigid posture, mask-like face, slow movements and a shuffling, unbalanced walk, discoloration, numbness and pain in fingers or toes (Raynaud’s phenomenon).

-        Concentrated urine (dark in colour), feel or are sick, have muscle cramps, confusion and fits which may be due to inappropriate ADH (anti-diuretic hormone) secretion can occur with ACE inhibitors. If you have these symptoms contact your doctor as soon as possible.

 Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

You can also report side effects directly via the national reporting system.

·       Keep this medicine out of the sight and reach of children.

·       Do not store above 30C.

·       Do not use this medicine after the expiry date which is stated on the carton and bottle. The expiry date refers to the last day of that month.

·       Keep the bottle tightly closed in order to protect from moisture. Store in the original package.

·       Do not throw away any medicine via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer used. These measures will help protect the environment.